A prospective evaluation of the risk of QT prolongation with hormone replacement therapy: The atherosclerosis risk in communities study

PURPOSE: Prolongation of the QT interval is associated with an increased risk of arrhythmia, coronary heart disease (CHD), and mortality. Estrogens and androgens have been proposed as a causal factor in QT lengthening. We tested whether postmenopausal hormone replacement therapy was associated with prolonged QT intervals in a healthy population sample of women (mean age = 54). METHODS: Women (n = 3,103) were asked about estrogen (ERT) and progestin plus estrogen (PERT) replacement therapy use at 4 examinations over 9 years. Electrocardiographic QT intervals were measured and corrected for heart rate using the QT Index (QTI) and Bazett's correction. QT prolongation was defined as QTI > 110% and a change from baseline of ≥4%. RESULTS: Heart rate corrected QT length was moderately but significantly (p<0.01) greater, and the risk of QT prolongation was nearly twice (Odds Ratio = 1.9, 95% Confidence Interval: 1.2-2.0) that in women who used ERT compared with never users. PERT use was not significantly associated with QT length. CONCLUSIONS: The potential for slight increases in QT length over time, and an increased risk of QT prolongation with ERT use identified in this observational study, are important concerns that should be further explored in randomized trials.